Production of polyunsaturated fatty acids in oleaginous yeasts

Abstract

The present invention relates to methods for the production of ω-3 and / or ω-6 fatty acids in oleaginous yeast. Thus, desaturases and elongases able to catalyze the conversion of linoleic acid (LA) to γ-linolenic acid (GLA); α-linoleic acid (ALA) to stearidonic acid (STA); GLA to dihomo-γ-linoleic acid (DGLA); STA to eicosatetraenoic acid (ETA); DGLA to arachidonic acid (ARA); ETA to eicosapentaenoic acid (EPA); DGLA to ETA; EPA to docosapentaenoic acid (DPA); and ARA to EPA have been introduced into the genome of Yarrowia for synthesis of ARA and EPA.

Description

[0001]This application claims the benefit of U.S. Provisional Application No. 60 / 468677, filed May 7, 2003.FIELD OF THE INVENTION[0002]This invention is in the field of biotechnology. More specifically, this invention pertains to the production of long chain polyunsaturated fatty acids (PUFAs) in oleaginous yeasts.BACKGROUND OF THE INVENTION[0003]It has long been recognized that certain polyunsaturated fatty acids, or PUFAs, are important biological components of healthy cells. For example, such PUFAs are recognized as:[0004]“Essential” fatty acids that can not be synthesized de novo in mammals and instead must be obtained either in the diet or derived by further desaturation and elongation of linoleic acid (LA) or α-linolenic acid (ALA);[0005]Constituents of plasma membranes of cells, where they may be found in such forms as phospholipids or triglycerides;[0006]Necessary for proper development, particularly in the developing infant brain, and for tissue formation and repair; and,[0...

AI Technical Summary

Benefits of technology

"The present invention provides methods for producing ω-3 and ω-6 fatty acids in an oleaginous yeast host. This is achieved by providing an oleaginous yeast with a functional ω-3 / ω-6 fatty acid biosynthetic pathway and growing it in the presence of a fermentable carbon source. The method can also be used to produce specific ω-6 fatty acids such as linoleic acid, γ-linolenic acid, dihomo-γ-linoleic acid, and arachidonic acid, as well as specific ω-3 fatty acids such as α-linoleic acid, stearidonic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid."

Problems solved by technology

Despite a variety of commercial sources of PUFAs from natural sources, there are several disadvantages associated with these methods of production.

First, natural sources such as fish and plants tend to have highly heterogeneous oil compositions.

Fish oils commonly have unpleasant tastes and odors, which may be impossible to separate economically from the desired product and can render such products unacceptable as food supplements.

Unpleasant tastes and odors can make medical regimens based on ingestion of high dosages undesirable, and may inhibit compliance by the patient.

Furthermore, fish may accumulate environmental pollutants and ingestion of fish oil capsules as a dietary supplement may result in ingestion of undesired contaminants.

Natural sources are also subject to uncontrollable fluctuations in availability (e.g., due to weather, disease, or over-fishing in the case of fish stocks); and, crops that produce PUFAs often are not competitive economically with hybrid crops developed for food production.

Large-scale fermentation of some organisms that naturally produce PUFAs (e.g., Porphyridium, Mortierella) can also be expensive and / or difficult to cultivate on a commercial scale.

However, these efforts have proved largely unsuccessful in improving yield of oil or the ability to control the characteristics of the oil composition produced.

Although advances in the art of genetic engineering have been made, such techniques have not been developed for oleaginous yeasts.

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